Severe Aplastic Anemia, Refractory Clinical Trial
Official title:
A Pilot Study of Alemtuzumab (Campath) in Patients With Relapsed or Refractory Severe Aplastic Anemia
| Verified date | October 2018 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study will evaluate the safety and usefulness of a new immunosuppressive drug,
alemtuzumab (Campath ), in patients with severe aplastic anemia (SAA). SAA is a rare and
serious blood disorder in which the bone marrow stops making red blood cells, white blood
cells and platelets. Alemtuzumab is a monoclonal antibody that attaches to and kills white
blood cells called lymphocytes. In certain types of aplastic anemia, lymphocytes are
responsible for the destruction of stem cells in the bone marrow, leading to a decrease in
blood counts. Because alemtuzumab destroys lymphocytes, it may be effective in treating
aplastic anemia. Alemtuzumab is currently approved to treat chronic lymphocytic leukemia and
is also helpful in other conditions that require immunosuppression, such as rheumatoid
arthritis and immune cytopenias.
Patients 2 years of age and older with severe aplastic anemia whose disease does not respond
to immunosuppressive therapy or has recurred following immunosuppressive therapy may be
eligible for this study. Participants undergo the following tests and procedures:
- Pretreatment evaluation: Patients have a medical history, physical examination, blood
tests, electrocardiogram (EKG), echocardiogram, 24-hour Holter monitor (continuous
24-hour monitoring of electrical activity of the heart), bone marrow biopsy (withdrawal
through a needle of a small sample of bone marrow for analysis).
- Placement of a central line, if needed: An intravenous line (tube) is placed into a
major vein in the patient's chest. It can stay in the body for the entire treatment
period and be used to give chemotherapy or other medications, including antibiotics and
blood transfusions, if needed, and to withdraw blood samples.
- Alemtuzumab therapy: Patients are admitted to the NIH Clinical Center for the first few
injections for close monitoring of side effects. After receiving an initial small test
dose, patients begin the first of ten daily injections under the skin, each lasting
about 2 hours. Once patients tolerate the infusions with minimal or no side effects,
they may be given the remaining infusions on an outpatient basis. Patients who relapse
after their initial response to alemtuzumab are given cyclosporine to see if this drug
will boost their immune response.
- Patients receive transfusions, growth factors, and antibiotic therapy, as needed.
- Infection therapy: Patients are given aerosolized pentamidine to protect against lung
infections and valacyclovir to protect against herpes infections.
- A blood test is done and vital signs are measured every day while patients receive
alemtuzumab.
- Patients have an echocardiogram and 24-hour Holter monitor after the last dose of
alemtuzumab.
- Blood tests are done weekly for the first 3 months after alemtuzumab administration,
then every other week until 6 months.
Patients return to the NIH for follow-up visits 1 month, 3 months, 6 months, and yearly for 5
years after the last dose of alemtuzumab for the following tests and evaluations:
- Blood test
- Repeat echocardiogram at 3-month visit
- Repeat bone marrow biopsy 6 months and 12 months after alemtuzumab, then as clinically
indicated for 5 years.
| Status | Completed |
| Enrollment | 47 |
| Est. completion date | October 15, 2018 |
| Est. primary completion date | April 14, 2014 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years to 110 Years |
| Eligibility |
- INCLUSION CRITERIA: Relapsed severe aplastic anemia after initial hematologic response to a prior course of h-ATG or r-ATG based immunosuppression Or Refractory severe aplastic anemia not responding to both horse-ATG and rabbit ATG-based immunosuppression The criteria for severe aplastic anemia are two of the three criteria: - Absolute neutrophil count less than or equal to 500 /mm(3) - Platelets to less than or equal to 20,000/mm(3) - Absolute reticulocyte count less than 60,000 /microL Age greater than or equal to 2 years old and greater than 12 kg Prospective subjects or their parent(s)/responsible guardian(s) must be able to comprehend and be willing to sign an informed consent. EXCLUSION CRITERIA: Known Diagnosis of Fanconi's anemia Evidence of a clonal disorder on cytogenetics. In the refractory disease setting, prospective subjects with super severe neutropenia (ANC less than 200 /microL) will not be excluded if results of cytogenetics are not available or pending. Infection not adequately responding to appropriate therapy HIV positivity Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old Man's Beard) within 2 weeks of enrollment Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy, or that death within 7-10 days is likely Previous hypersensitivity to alemtuzumab or its components Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential Not able to understand the investigational nature of the study or give informed consent |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. Review. — View Citation
Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. Review. — View Citation
Zoumbos NC, Gascón P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Hematological Response at 6 Months | Hematological response is defined as no longer satisfying blood count criteria for Severe Aplastic Anemia. Patients were classified as responders if they met two of the following three criteria: ANC greater than 500/ mm'; platelet count greater than 20,000/mm3; and reticulocyte count greater than 40,000/mm3 (60,000/mm3 after January 1993). | 6 months |